Update: The following update relating to this announcement has been issued:

January 21, 2011 - See Notice NOT-HG-11-009 Notice of Amendment and Re-issuance of Administrative Supplements for the Addition of Standard Measures to Population-based Genomic Research: The PhenX Toolkit.

National Human Genome Research Institute (NHGRI)
Office of Behavioral and Social Sciences Research (OBSSR)

Purpose

The National Human Genome Research Institute (NHGRI) along
with the Office of Behavioral and Social Sciences Research (OBSSR) announces an
Administrative Supplement Program to promote the inclusion of standard
phenotypic and environmental exposure measures selected from the PhenX Toolkit
(www.phenxtoolkit.org) into existing
population-based genomic studies supported by the NIH. The goals of this supplement
program are to evaluate the usefulness of PhenX measures and to stimulate their
uptake into population studies to enhance genomic research. The inclusion of
measures from the PhenX Toolkit will enable researchers to broaden the scope of
their studies, examine additional genetic and environmental factors
contributing to human health and disease, and combine their studies with other
investigators using the same measures to increase power and efficiency of
genomic discovery.

Background

Genome-wide association (GWA) studies have identified
hundreds of associations between genetic variants and complex human diseases,
and for some diseases, such as diabetes and Crohn’s disease, pooling of
multiple GWA studies by meta-analysis has led to the discovery of new gene
associations. However, most GWA studies have had relatively few phenotypic and
exposure measures in common. Harmonizing data across studies that have used
disparate measures to collect similar information is difficult and time
consuming. Development and adoption of standard phenotypic and exposure
measures could facilitate the creation of larger, more comprehensive datasets
with a variety of phenotype and exposure data for cross-study analysis, thus
increasing statistical power and the ability to detect associations of modest
effect sizes and gene-gene and gene-environment interactions.

Recognizing the need for standard phenotypic and exposure
measures, particularly as related to GWA studies, NHGRI initiated the PhenX
Toolkit in 2006 through RFA-HG-00-006, “High-Priority Phenotype and Exposure
Measures for Cross-Study Analysis in Genome-Wide Association Studies.” The goal
of this three-year program was to identify and catalogue 15 high-quality,
well-established, and broadly applicable measures for each of 21 research
domains for use in GWA studies and other large-scale genomic research. A PhenX
domain is a topic area with a unifying theme such as Demographics,
Anthropometrics, Neurology, Cancer, or Social Environments. PhenX measures are
selected by Working Groups of domain experts using a consensus process and are
made available to the scientific community via the PhenX Toolkit (www.phenxtoolkit.org).

Although PhenX is on track to meet its three-year goal of
producing 15 measures in each of 21 domains, many of the domains have been
released relatively recently and experience has not been sufficient to gauge
the impact of the Toolkit nor potential needs for its continuation. NHGRI has
been urged to catalyze adoption of PhenX measures in ongoing genomic studies to
obtain timely and needed feedback on the value of the resource including gaps
in measures, ease of use, and overall usefulness of the PhenX Toolkit for the
research community.

This Notice announces the availability of administrative
supplements to existing NIH-funded projects to support the incorporation of a
minimum of 8-10 PhenX measures into existing population-based genomic research
studies that aim to identify the genetic and environmental factors that
contribute to health and the development of complex disease. Principal
Investigators (PIs) are strongly encouraged to select PhenX measures that are
broadly related to a variety of complex traits (e.g., substance use, physical
activity, height, weight, etc.) and not just measures related to the primary
phenotypes being evaluated in the parent study. Individual-level phenotypic
and exposure data collected using PhenX measures, along with previously
generated genetic data, will be made available to the broader research
community through the National Center for Biotechnology Information's Database
of Genotypes and Phenotypes (dbGaP).

PIs should budget for themselves and a data analyst to
travel to the Washington, DC area shortly after award for a grantee meeting
where they will work together with NHGRI and the PhenX Toolkit grantee, RTI
International, to decide upon metrics that will allow a thorough evaluation of
the functionality and utility of the PhenX Toolkit, agree upon common approaches
for describing and analyzing data collected using the PhenX measures, and
identify potential cross-study analyses that can be conducted by the entire set
or subsets of PIs. RTI will serve as a facilitator, and if desired, a
collaborator in effective incorporation and use of PhenX measures. At a second
grantee meeting near the end of the supplement period, PIs will be expected to
report findings from analyses of both individual projects and cross-study
collaborations and to provide feedback to NHGRI based on the agreed-upon
metrics.

Budget and Funding Information

A total of $1M is anticipated to be provided in Fiscal Year
2011 to support 6-10 supplements for a project duration of one year.

Administrative supplements are limited to $100,000 in direct costs.

Eligibility

This announcement is for supplements to NIH grants meeting
the selection criteria outlined in the section titled "Selection."
The grant must have at least one year remaining at the time the award is made.

To be eligible, the PI must be able to demonstrate that the
PhenX measures can be administered to participants within the first three
months of the award to ensure that data collection and analysis will be
completed by the end of the supplement period. Studies should include at least
1,000 participants with previously generated genotype data whom have been
adequately consented for sharing of both genomic and phenotypic data with the
broader research community for a variety of research purposes. Priority will
be given to studies with higher numbers of participants.

To be
eligible, the parent grant must be active, and the research proposed in the
supplement must be accomplished within the competitive segment. The proposed
supplement must be within the general scope of the peer-reviewed activities and
aims approved within the parent grant.

IMPORTANT: The research proposed by the NIH grantee in the supplement
application must be within the original scope of the NIH-supported grant
project. The funding mechanism being used to support this program,
administrative supplements, can be used to cover cost increases that are
associated with achieving certain new research objectives as long as they are
within the original scope of the project. Any cost increases need to result from
making modifications to the project in order to take advantage of opportunities
that would increase the value of the project consistent with its originally
approved objectives and purposes.

Submitting an Administrative Supplement Request

To be considered for an administrative supplement, the
request must be signed by the Authorized Organizational Representative/Signing
Official (AOR/SO), and must describe the need for additional funding and the
categorical costs.

Submit (1) one original, hard copy of the request packet (with original
signatures of the authorized business official) and (2) an electronic copy of
the submitted supplement request as a single email attachment in PDF format to
the contact listed below:

Requests should be submitted on the PHS398
Application Guide forms (font size and other formatting rules apply as designated
in the instructions), as indicated below. Include only the following elements:

Cover
Letter which cites this Notice, and the following information:

Project Director/Principal Investigator (PD/PI) name

Parent grant number and title

Amount of the requested supplement

Name and title of the institutional official, and

Phone, email, and address information for both the PD/PI and
institutional official.

The cover letter must be signed by the authorized organizational
representative/institutional official.

PHS
398 Form Page 1 (Face page)

The title of the project should be the title of the parent award.

This Notice should be cited in Box 2, and the “yes” box should be
checked.

The Principal Investigator (PI) must be the same as the PI on the
parent award. For Multiple PI parent awards, the Contact PI must be the
PI listed on the supplement request, and the supplement cannot change the
Multiple PI team.

The remaining items on the face page should be filled out in
accordance with the PHS 398 application instructions.

PHS
398 Form Page 2

Note: The project “summary” is that of the administrative
supplement, not the parent grant.

A
brief proposal describing the project, including:

Scope of the overall project and the anticipated contribution of the
requested supplement (not to exceed five pages).

Provide a brief description of the scope of the overall project
on which the supplemental request is based.

This section should include a description of the supplement's
specific aims, including research design and methods and data analysis.
Describe the relationship of the supplement request to the parent grant.

Budget for the supplement with a justification that details the
items requested, including Facilities and Administrative costs.

Biographical Sketch for all new key personnel(those who
are additions on the supplemental project

Human Subjects documentation (if applicable).

Include a current Human Subjects/IRB approval letter, if
available. Otherwise, this will be required at the time of funding. All
appropriate IRB approvals must be in place prior to a supplement award being
made.

Any differences in the involvement or use of human subjects or
specimens between the administrative supplement activity and the parent grant
should be noted.

When appropriate, details should be provided on the protection of
human subjects and inclusion of women, children, and minorities.
Additional guidance on Human Subjects Research is provided under Part II of the
PHS 398 instructions.

PHS 398 Checklist Form

Selection

Administrative supplement requests will be reviewed
administratively by NIH Staff. Selection factors will include the following:

Relevance of the proposed activities to the parent grant

Adequate progress of the parent grant appropriate to the current
stage of the project

Appropriate and well-described plan to accomplish the goals
within the timeframe proposed including a plan demonstrating that the PhenX
measures can be administered to study participants within the first three
months of award to ensure that data collection and analysis can be completed
within one year

Appropriateness of the selected measures for the study population

Population diversity, particularly in regard to children and
minority populations with important health disparities

Public health importance of the traits being studied

Availability of high-quality genotyping data (approximately
>2,000 variants) in at least 1,000 participants although higher numbers of
participants will be given priority